CN112479992A - Preparation method of 2-hydroxy-5-bromo-4-trifluoromethylpyridine - Google Patents

Preparation method of 2-hydroxy-5-bromo-4-trifluoromethylpyridine Download PDF

Info

Publication number
CN112479992A
CN112479992A CN202011387978.XA CN202011387978A CN112479992A CN 112479992 A CN112479992 A CN 112479992A CN 202011387978 A CN202011387978 A CN 202011387978A CN 112479992 A CN112479992 A CN 112479992A
Authority
CN
China
Prior art keywords
bromo
trifluoromethylpyridine
hydroxy
reaction
methylpyridine
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
CN202011387978.XA
Other languages
Chinese (zh)
Inventor
廖明
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nanjing Mairuimi Biotechnology Co ltd
Original Assignee
Nanjing Mairuimi Biotechnology Co ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Nanjing Mairuimi Biotechnology Co ltd filed Critical Nanjing Mairuimi Biotechnology Co ltd
Priority to CN202011387978.XA priority Critical patent/CN112479992A/en
Publication of CN112479992A publication Critical patent/CN112479992A/en
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/64—One oxygen atom attached in position 2 or 6

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pyridine Compounds (AREA)

Abstract

The invention discloses a preparation method of 2-hydroxy-5-bromo-4-trifluoromethylpyridine, which comprises the following steps: taking formaldehyde, acetaldehyde and ammonia, carrying out high-temperature condensation reaction to obtain a 3-methylpyridine crude product, and carrying out rectification separation to obtain the required 3-methylpyridine; vaporizing the 3-methylpyridine, and reacting in a bromine gas atmosphere to obtain a crude product of 5-bromo-4-tribromomethylpyridine; melting the crude product of 5-bromo-4-tribromomethylpyridine, and substituting fluorine to obtain 5-bromo-4-trifluoromethylpyridine; reacting 5-bromo-4-trifluoromethylpyridine under the action of concentrated ammonia to obtain 2-hydroxy-5-bromo-4-trifluoromethylpyridine. The 2-hydroxy-5-bromo-4-trifluoromethylpyridine prepared by the method is simple to prepare and high in purity.

Description

Preparation method of 2-hydroxy-5-bromo-4-trifluoromethylpyridine
Technical Field
The invention belongs to the field of pharmaceutical chemistry, and particularly relates to a preparation method of 2-hydroxy-5-bromo-4-trifluoromethylpyridine.
Background
2-hydroxy-5-bromo-4-trifluoromethylpyridine of the formula C6H3BrF3NO is an important intermediate for synthesizing a plurality of medicines, large-scale production is difficult to realize at present, and meanwhile, in the preparation process, the working procedure is complex, the purity of the product is low, and a plurality of byproducts are generated. Therefore, a fast, simple and efficient preparation method of 2-hydroxy-5-bromo-4-trifluoromethylpyridine is urgently needed.
Disclosure of Invention
The invention aims to provide a preparation method of 2-hydroxy-5-bromo-4-trifluoromethylpyridine, so that the 2-hydroxy-5-bromo-4-trifluoromethylpyridine can be rapidly prepared, and the preparation method is high in purity and stable in performance.
The technical scheme of the invention is realized through the following aspects:
a method for preparing 2-hydroxy-5-bromo-4-trifluoromethylpyridine, comprising the steps of:
s1: taking formaldehyde, acetaldehyde and ammonia, carrying out high-temperature condensation reaction to obtain a 3-methylpyridine crude product, and carrying out rectification separation to obtain the required 3-methylpyridine;
s2: vaporizing the 3-methylpyridine prepared in the step S1, and reacting in a bromine atmosphere to obtain a crude product of 5-bromo-4-tribromomethylpyridine;
s3: melting the crude product of 5-bromo-4-tribromomethylpyridine prepared in the step S2, and substituting fluorine to obtain 5-bromo-4-trifluoromethylpyridine;
s4: and (4) reacting the 5-bromo-4-trifluoromethylpyridine prepared in the step (S3) under the action of concentrated ammonia to obtain the 2-hydroxy-5-bromo-4-trifluoromethylpyridine.
Further, in the step S1, the reaction temperature is 400-430 ℃.
Further, in the step S2, the temperature of the vaporization reaction is 140-150 ℃.
Further, in the step S3, the raw material substituted by fluorine is hydrogen fluoride, and the temperature of the melting reaction is 180-.
Further, in the step S4, the reaction temperature of the concentrated ammonia reaction is 350-380 ℃.
Detailed Description
In order to make the technical means, the creation characteristics, the achievement purposes and the effects of the invention easy to understand, the invention is further described with the specific embodiments.
Example 1
A method for preparing 2-hydroxy-5-bromo-4-trifluoromethylpyridine, comprising the steps of:
s1: taking formaldehyde, acetaldehyde and ammonia, carrying out high-temperature condensation reaction to obtain a 3-methylpyridine crude product, and carrying out rectification separation to obtain the required 3-methylpyridine;
s2: vaporizing the 3-methylpyridine prepared in the step S1, and reacting in a bromine atmosphere to obtain a crude product of 5-bromo-4-tribromomethylpyridine;
s3: melting the crude product of 5-bromo-4-tribromomethylpyridine prepared in the step S2, and substituting fluorine to obtain 5-bromo-4-trifluoromethylpyridine;
s4: and (4) reacting the 5-bromo-4-trifluoromethylpyridine prepared in the step (S3) under the action of concentrated ammonia to obtain the 2-hydroxy-5-bromo-4-trifluoromethylpyridine.
In step S1, the reaction temperature was 400 ℃.
In step S2, the temperature of the vaporization reaction was 140 ℃.
In step S3, the raw material substituted with fluorine is hydrogen fluoride, and the temperature of the melting reaction is 180 ℃.
In step S4, the reaction temperature of the concentrated ammonia reaction is 350 ℃.
Example 2
A method for preparing 2-hydroxy-5-bromo-4-trifluoromethylpyridine, comprising the steps of:
s1: taking formaldehyde, acetaldehyde and ammonia, carrying out high-temperature condensation reaction to obtain a 3-methylpyridine crude product, and carrying out rectification separation to obtain the required 3-methylpyridine;
s2: vaporizing the 3-methylpyridine prepared in the step S1, and reacting in a bromine atmosphere to obtain a crude product of 5-bromo-4-tribromomethylpyridine;
s3: melting the crude product of 5-bromo-4-tribromomethylpyridine prepared in the step S2, and substituting fluorine to obtain 5-bromo-4-trifluoromethylpyridine;
s4: and (4) reacting the 5-bromo-4-trifluoromethylpyridine prepared in the step (S3) under the action of concentrated ammonia to obtain the 2-hydroxy-5-bromo-4-trifluoromethylpyridine.
In step S1, the reaction temperature was 430 ℃.
In step S2, the temperature of the vaporization reaction was 150 ℃.
In step S3, the raw material substituted with fluorine is hydrogen fluoride, and the temperature of the melting reaction is 120 ℃.
In step S4, the reaction temperature of the concentrated ammonia reaction is 380 ℃.
Example 3
A method for preparing 2-hydroxy-5-bromo-4-trifluoromethylpyridine, comprising the steps of:
s1: taking formaldehyde, acetaldehyde and ammonia, carrying out high-temperature condensation reaction to obtain a 3-methylpyridine crude product, and carrying out rectification separation to obtain the required 3-methylpyridine;
s2: vaporizing the 3-methylpyridine prepared in the step S1, and reacting in a bromine atmosphere to obtain a crude product of 5-bromo-4-tribromomethylpyridine;
s3: melting the crude product of 5-bromo-4-tribromomethylpyridine prepared in the step S2, and substituting fluorine to obtain 5-bromo-4-trifluoromethylpyridine;
s4: and (4) reacting the 5-bromo-4-trifluoromethylpyridine prepared in the step (S3) under the action of concentrated ammonia to obtain the 2-hydroxy-5-bromo-4-trifluoromethylpyridine.
In step S1, the reaction temperature was 410 ℃.
In step S2, the temperature of the vaporization reaction was 145 ℃.
In step S3, the raw material substituted with fluorine is hydrogen fluoride, and the temperature of the melting reaction is 190 ℃.
In step S4, the reaction temperature of the concentrated ammonia reaction is 360 ℃.
Example 4
A method for preparing 2-hydroxy-5-bromo-4-trifluoromethylpyridine, comprising the steps of:
s1: taking formaldehyde, acetaldehyde and ammonia, carrying out high-temperature condensation reaction to obtain a 3-methylpyridine crude product, and carrying out rectification separation to obtain the required 3-methylpyridine;
s2: vaporizing the 3-methylpyridine prepared in the step S1, and reacting in a bromine atmosphere to obtain a crude product of 5-bromo-4-tribromomethylpyridine;
s3: melting the crude product of 5-bromo-4-tribromomethylpyridine prepared in the step S2, and substituting fluorine to obtain 5-bromo-4-trifluoromethylpyridine;
s4: and (4) reacting the 5-bromo-4-trifluoromethylpyridine prepared in the step (S3) under the action of concentrated ammonia to obtain the 2-hydroxy-5-bromo-4-trifluoromethylpyridine.
In step S1, the reaction temperature was 420 ℃.
In step S2, the temperature of the vaporization reaction was 145 ℃.
In step S3, the raw material substituted with fluorine is hydrogen fluoride, and the temperature of the melting reaction is 185 ℃.
In step S4, the reaction temperature of the concentrated ammonia reaction was 370 ℃.
Example 5
A method for preparing 2-hydroxy-5-bromo-4-trifluoromethylpyridine, comprising the steps of:
s1: taking formaldehyde, acetaldehyde and ammonia, carrying out high-temperature condensation reaction to obtain a 3-methylpyridine crude product, and carrying out rectification separation to obtain the required 3-methylpyridine;
s2: vaporizing the 3-methylpyridine prepared in the step S1, and reacting in a bromine atmosphere to obtain a crude product of 5-bromo-4-tribromomethylpyridine;
s3: melting the crude product of 5-bromo-4-tribromomethylpyridine prepared in the step S2, and substituting fluorine to obtain 5-bromo-4-trifluoromethylpyridine;
s4: and (4) reacting the 5-bromo-4-trifluoromethylpyridine prepared in the step (S3) under the action of concentrated ammonia to obtain the 2-hydroxy-5-bromo-4-trifluoromethylpyridine.
In step S1, the reaction temperature was 415 ℃.
In step S2, the temperature of the vaporization reaction was 150 ℃.
In step S3, the raw material substituted with fluorine is hydrogen fluoride, and the temperature of the melting reaction is 195 ℃.
In step S4, the reaction temperature of the concentrated ammonia reaction was 370 ℃.
It will be appreciated by those skilled in the art that the invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The embodiments disclosed above are therefore to be considered in all respects as illustrative and not restrictive. All changes which come within the scope of or equivalence to the invention are intended to be embraced therein.

Claims (5)

1. A preparation method of 2-hydroxy-5-bromo-4-trifluoromethylpyridine is characterized by comprising the following steps:
s1: taking formaldehyde, acetaldehyde and ammonia, carrying out high-temperature condensation reaction to obtain a 3-methylpyridine crude product, and carrying out rectification separation to obtain the required 3-methylpyridine;
s2: vaporizing the 3-methylpyridine prepared in the step S1, and reacting in a bromine atmosphere to obtain a crude product of 5-bromo-4-tribromomethylpyridine;
s3: melting the crude product of 5-bromo-4-tribromomethylpyridine prepared in the step S2, and substituting fluorine to obtain 5-bromo-4-trifluoromethylpyridine;
s4: and (4) reacting the 5-bromo-4-trifluoromethylpyridine prepared in the step (S3) under the action of concentrated ammonia to obtain the 2-hydroxy-5-bromo-4-trifluoromethylpyridine.
2. The process according to claim 1 for the preparation of 2-hydroxy-5-bromo-4-trifluoromethylpyridine, wherein: in the step S1, the reaction temperature is 400-430 ℃.
3. The process according to claim 1 for the preparation of 2-hydroxy-5-bromo-4-trifluoromethylpyridine, wherein: in the step S2, the temperature of the vaporization reaction is 140-150 ℃.
4. The process according to claim 1 for the preparation of 2-hydroxy-5-bromo-4-trifluoromethylpyridine, wherein: in the step S3, the raw material substituted by fluorine is hydrogen fluoride, and the temperature of the melting reaction is 180-.
5. The process according to claim 1 for the preparation of 2-hydroxy-5-bromo-4-trifluoromethylpyridine, wherein: in the step S4, the reaction temperature of the concentrated ammonia reaction is 350-380 ℃.
CN202011387978.XA 2020-12-01 2020-12-01 Preparation method of 2-hydroxy-5-bromo-4-trifluoromethylpyridine Withdrawn CN112479992A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202011387978.XA CN112479992A (en) 2020-12-01 2020-12-01 Preparation method of 2-hydroxy-5-bromo-4-trifluoromethylpyridine

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202011387978.XA CN112479992A (en) 2020-12-01 2020-12-01 Preparation method of 2-hydroxy-5-bromo-4-trifluoromethylpyridine

Publications (1)

Publication Number Publication Date
CN112479992A true CN112479992A (en) 2021-03-12

Family

ID=74938849

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202011387978.XA Withdrawn CN112479992A (en) 2020-12-01 2020-12-01 Preparation method of 2-hydroxy-5-bromo-4-trifluoromethylpyridine

Country Status (1)

Country Link
CN (1) CN112479992A (en)

Similar Documents

Publication Publication Date Title
CN113582874B (en) Synthesis method of bromoacetonitrile
CN101108821B (en) Method of manufacturing 2-picoline
CN113929711A (en) Preparation method of lithium difluoroborate
CN112479992A (en) Preparation method of 2-hydroxy-5-bromo-4-trifluoromethylpyridine
CN113336655A (en) Preparation method of (R) -3-aminobutanol
CN110878104B (en) Preparation method of chiral 1, 2-bis (2, 5-diphenylphosphino) ethane
CN111320535B (en) Preparation method of 3- (benzyloxy) -1-cyclobutanone
CN116655529A (en) Method for synthesizing 3-aryl quinoline compound by nickel catalysis
CN116143088A (en) Preparation method of difluoro-sulfonyl imide and difluoro-sulfonyl imide lithium
CN105566257A (en) Industrial preparation method of acetyl tetrahydrofuran with high optical purity
CN115818714A (en) Method for preparing potassium heptafluoroniobate
CN112194585B (en) Synthetic method of bromhexine hydrochloride
CN113861034A (en) Preparation method of 2-fluoro-3-nitrobenzoic acid
CN113582805A (en) Production process for producing high-purity 2, 4-dichlorofluorobenzene by taking o-dichlorobenzene as raw material
CN112321495A (en) Preparation method of 2-fluoro-5- (trifluoromethyl) pyridine
CN107118183B (en) Synthesis method of tetrahydro-3-furanmethanol
CN111592559A (en) Method for synthesizing sodium difluorooxalate through one-step method
CN113582852A (en) Method for producing dinitroaniline
CN111217690A (en) Preparation method of propafenone hydrochloride and intermediate 2' -hydroxy dihydrochalcone thereof
CN112608259B (en) Synthetic method of 3-mercaptopropionic acid
CN114621185B (en) Synthesis method of raceme nicotine
CN116947610A (en) New synthetic route for cyclobutanone
CN116874420B (en) Preparation method of lenvatinib intermediate 4-chloro-7-methoxyquinoline-6-amide
CN105753804A (en) Method of preparing 3-morpholinone
CN117886732A (en) Preparation method of 1, 5-dimethyl-2-pyrrolidone

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
WW01 Invention patent application withdrawn after publication

Application publication date: 20210312

WW01 Invention patent application withdrawn after publication